title: Long-term stabilization effects of leptin on brain functions in a leptin-deficient patient.
abstract: BACKGROUND
  Congenital leptin deficiency, caused by a very rare mutation in the gene encoding leptin, leads to severe obesity, hyperphagia and impaired satiety. The only systemic treatment is the substitution with metreleptin leading to weight reduction based on hormonal changes. Several studies have also shown alterations in brain function after metreleptin therapy. In a previous study, we were able to show changes in homeostatic (hypothalamus) and reward-related brain areas (striatum, orbitofrontal cortex (OFC), substantia nigra/ventral tegmental area, amygdala) 3 days and 6 months after therapy start in a leptin-deficient adolescent girl. To further access the time course of functional brain activation changes, we followed the patient for 2 years after initiation of the therapy. DESIGN, PATIENT: Functional magnetic resonance imaging during visual stimulation with food (high- and low-caloric) and non-food pictures was performed 1 and 2 years after therapy start in the previously described patient.
  
  
  RESULTS
  The comparison of 'food vs. non-food' pictures showed a stabilization of the long-term effects in the amygdala and in the OFC. Therefore, no significant differences were observed between 6 months compared to 12 and 24 months in these regions. Additionally, a reduction of the frontopolar cortex activity over the whole time span was observed. For the comparison of high- and low-caloric pictures, long-term effects in the hypothalamus showed an assimilating pattern for the response to the food categories whereas only acute effects after 3 months were observed in hedonic brain regions.
  
  
  CONCLUSIONS
  This follow-up study shows that the long lasting benefit of metreleptin therapy is also associated with activation changes in homeostatic, hedonic and frontal control regions in congenital leptin deficiency.
authors.affiliation: Institute of Medical Psychology and Behavioral Neurobiology, fMEG Center, University of Tübingen, Tübingen, Germany. sabine.frank@med.uni-tuebingen.de
authors.forename: Sabine
authors.initials: S
authors.lastname: Frank
authors.forename: Martin
authors.initials: M
authors.lastname: Heni
authors.forename: Anja
authors.initials: A
authors.lastname: Moss
authors.forename: Julia
authors.initials: J
authors.lastname: von Schnurbein
authors.forename: Sadaf
authors.initials: S
authors.lastname: Farooqi
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Hubert
authors.initials: H
authors.lastname: Preissl
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
mesh_terms: D000293:Adolescent; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D006815:Hunger / Q000187:drug effects*; D020738:Leptin / Q000031:analogs & derivatives* / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D059906:Neuroimaging; D009765:Obesity / Q000151:congenital / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D010775:Photic Stimulation
chemical_list: D020738:Leptin; C415771:metreleptin